Factors having effects on sensitivity and/or resistance of cancer cells to anticancer drugs are changes in a mechanism for excretion of such drug extracellularly, drug metabolism, DNA repair, PI3K-Akt pathway, and apoptotic pathway, for example. In particular, it is known that in many anticancer-drug-resistant cancer cells, accumulation of anticancer drugs decreases, and the expression of P-glycoprotein actively pumping out wide-ranging anticancer drugs extracellularly or of a multidrug (anticancer drug) resistance-related protein, MRP1, increases in cell membranes. Several examples of conventional techniques have been reported, such as the in vitro introduction of a gene encoded to attenuate P-glycoprotein expression into anticancer-drug-resistant cancer cells, so as to attenuate the anticancer drug resistance of the cells (Masuda Y. et al., Cancer Chemother Pharmacol. 1998; 42(1):9-16; Wang F S. et al., Hum Gene Ther. 1999 May 1; 10 (7): 1185-95; Yague E. et al., Gene Ther. 2004 July; 11 (14): 1170-4). However, examples reported herein are the results of in vitro experiments, and in vivo usefulness has never been demonstrated with the use of animals. Also, even after the above reports, confirmation of the effects in vivo has never been reported.
Meanwhile, a REIC/Dkk-3 gene is known as a cell-immortalization-related gene. It has been reported that the expression of this gene is suppressed in cancer cells (International Patent Publication WO01/038523 Pamphlet; Tsuji, T. et al., BiochemBiophys Res Commun 268, 20-4 (2000); Tsuji, T. et al., BiochemBiophys Res Commun 289, 257-63 (2001); Nozaki, I. et al., Int J Oncol 19, 117-21 (2001); Kurose, K. et al., J Urol 171, 1314-8 (2004)).
The REIC/Dkk-3 gene is a member of the Dkk family, and it has been suggested that it inhibits Wnt signal transduction via a Wnt receptor (Bafico, A. et al., Nat Cell Biol 3, 683-6 (2001); Hoang, B. H. et al., Cancer Res 64, 2734-9 (2004)). It has been reported that the Wnt gene plays multiple roles in important biological events such as cell growth, differentiation, and canceration (Moon, R. T. et al., Science 296, 1644-6 (2002)). Therefore, the Dkk family (4 genes of which are currently known in humans) may be similarly responsible for important functions in cell growth, differentiation, and canceration, but most members thereof remain unelucidated.    Patent document 1 International Patent Publication WO01/038523 Pamphlet    Non-patent document 1 Masuda Y. et al., Cancer chemother Pharmacol. 1998; 42 (1): 9-16    Non-patent document 2 Wang F S. et al., Hum Gene Ther. 1999 May 1; 10 (7): 1185-95    Non-patent document 3 Yague E. et al., Gene Ther. 2004 July; 11 (14): 1170-4    Non-patent document 4 Tsuji, T. et al., BiochemBiophys Res Commun 268, 20-4 (2000)    Non-patent document 5 Tsuji, T. et al., BiochemBiophys Res Commun 289, 257-63 (2001)    Non-patent document 6 Nozaki, I. et al., Int J Oncol 19, 117-21 (2001)    Non-patent document 7 Kurose, K. et al., J Urol 171, 1314-8 (2004)    Non-patent document 8 Bafico, A. et al., Nat Cell Biol 3, 683-6 (2001)    Non-patent document 9 Hoang, B. H. et al., Cancer Res 64, 2734-9 (2004)    Non-patent document 10 Moon, R. T. et al., Science 296, 1644-6 (2002)